Aberrant skin conditions afflict millions of people worldwide. Patients suffering from a skin condition often experience pain and/or discomfort due to the condition. For some patients, the pain or discomfort can be quite severe. A patient's ability to sleep, perform routine tasks, and/or participate in certain sports can be affected by some skin conditions. In addition to physical ailments, skin conditions can have a detrimental affect on a patient's psychological wellbeing. For instance, some skin conditions cause unsightly sores on a patient's skin, causing some patients to avoid social interaction and/or become emotionally depressed. Rosacea is one such condition that can have psychological effects because it often causes red discoloration of the face and the appearance of unsightly, acne-like pimples.
One characteristic of numerous skin conditions is epidermal hyperplasia. Epidermal hyperplasia is an abnormal increase in the number of normal cells in normal arrangement in epidermal tissue. Research has demonstrated that excessive growth of keratinocyte cells is commonly associated with epidermal hyperplasia. It is postulated that epidermal hyperplasia involves a complex multi-cellular inflammatory event. However, topical treatment of all-trans retinoic acid (RA) or its precursor, all-trans retinol (ROL), to the skin also results in epidermal hyperplasia. See, e.g., Varani J, et al., (2001) J. Invest. Dermatol, 117:1335-1341. Representative skin conditions associated with epidermal hyperplasia include psoriasis and atopic dermatitis. See, e.g., Krueger G C, et al., (1984) J. Am. Acad. Dermatol. 11: 937-947; Fry L. (1988), Brit. J. Dermatol. 119:445-461
Psoriasis is a chronic, inflammatory, hyperproliferative skin condition that affects approximately 2% of the general population. Approximately 150,000 new cases of psoriasis and approximately 400 deaths from psoriasis are reported each year. See Stem, R. S. (1995) Dermatol. Clin. 13:717-722. Typical symptoms of psoriasis include skin lesions, redness, inflammation, or patches of skin that become dry, red, covered with silvery scales, cracked, and/or painful. Additional symptoms include joint pain or aching, although these symptoms are typically associated with psoriatic arthritis. Psoriasis can affect all parts of the skin, but it is more commonly seen on the skin of the trunk, scalp, elbows, knees, or in the fingernails or toenails. The symptoms of psoriasis may become worse in response to cuts, burns, insect bites or other skin injuries. The symptoms of psoriasis can also be more severe in patients having a deficient immune system, such as patients afflicted with AIDS or receiving cancer chemotherapy.
There are a several of types of psoriasis. The most common type of psoriasis is chronic plaque syndrome. This type of psoriasis consists of periods of remission and relapse during the course of the condition. If left untreated, plaque psoriasis can evolve into a more severe condition, such as pustular psoriasis or erythrodermic psoriasis. In pustular psoriasis, the red areas on the skin contain blisters with pus. Erythrodermic psoriasis is characterized by large patches of skin that are red and scaling. Patients suffering from erythrodermic psoriasis often complain that the affected patches of skin are itchy and/or painful. Inverse psoriasis is characterized by smooth, inflamed areas of skin, typically appearing in skin folds. Guttate psoriasis appears as numerous, teardrop-shaped spots on the skin and is often associated with streptococcal throat infection. Nail psoriasis is characterized by changes in the finger and toe nails. This form of psoriasis often involves discoloring under the nail or thickening of the skin under the nail.
The current methods for treating psoriasis suffer from a number of drawbacks. For example, many of the currently-available, topical anti-psoriatic agents irritate the skin, cannot be used for extended durations, and/or lead to aggressive recurrence of the psoriatic condition if treatment is terminated abruptly. Anti-inflammatory agents, although capable of alleviating certain symptoms, do not cure the underlying disease. Another current treatment option, photochemotherapy, can lead to squamous-cell and melanoma skin cancer.
Accordingly, the need exists for new compositions and methods that are effective in treating skin conditions, such as psoriasis.